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spinqualitylabelsall models PDB ID 2zet Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
2zet, resolution 3.00Å ()
Ligands:	, , ,
Non-Standard Residues:
Gene:	Rab27b (Mus musculus), Slac2a (Mus musculus)
Structural annotation: Resources: InterPro : Ipr013753, Ipr001806, Ipr020851, Ipr005225, Ipr015597, Ipr003579, Ipr006788, Ipr010911, Ipr011011 Pfam : PF00071 UniProt : Q99P58, Q91V27
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, RCSB, PDBsum, TOPSAN
Coordinates:	save as pdb, mmCIF, xml

Contents 1 Structure 1.1 Structure of Rab27B 1.2 Strucure Slac2-a 2 References

Structure

Structure of Rab27B

General informations:

To obtain structural information on the complex of mouse Rab27B and Slac-a, a C-terminally truncated form of the GTPase-deficient mutant Rab27B (Q78L) was used. In fact, full size of Rab27B is 218 amino acids long whereas the truncated form of Rab27B contains only the GTPase domain (residues 1 to 201). ^{[1] [2]}

Detailed structure:

The structure of Rab27B in the complex contains a central six stranded beta sheet (ß1-6) flanked by five alpha helices (α1–5). Like other Ras-like small GTPases, Rab27B binds with GTP and Mg2+ in the conserved nucleotide-binding site (also see figure 2). Rab27B adopt a globular form in the complex. The ß2 and ß3 loop(residues 55-64) and α3-ß5 loop (residues122-126) of Rab27B are both regions involved in Slac2-a binding. ^[3]

The complex Rab27B/Slac2-a can only be formed when Rab27B is in a GTP form. This can be explain because of the changing of shape between Rab27B in the GTP and GDP form. (See figure 3) Rab27B–GTP adopts a compact monomer conformation, while an extended conformation was observed for GDP-bound Rab27B. Switch 1 and switch 2 of Rab27B play an important role in this changing of conformation. In fact, switch 1 and 2 allow GTP binding by making hydrogen bond with its γ-phosphate, and this way also allow Slac2-a binding.(see next paragraph) But in the complex Rab27B/GDP switch 1 and switch 2 exist completely apart from the bound GDP, so that there are no inter-actions with Slac2-a and no binding.

Strucure Slac2-a

General informations:

Slac2-a is a fragment from Slp Homology Domain, residues 1-146 from Melanophilin molecule. This protein is also called Exophilin-3. ^[4] Slac2-a plays an important role in actin-based melanosome transport in mammalian. In fact, the actin-binding domain of Slac2-a/Melanophilin is required for melanosome distribution in melanocytes.^[5]

To obtain structural information on the complex of mouse Rab27B/Slac2-a, a truncated form of Slac2-a was used. This fragment of Slac2-a is the minimum region (residue 1 to 146) of Slac2-a that specifically binds to the GTP-bound form of Rab27B.

Detailed structure:

The structure of the Slac2-a effector domain comprises three subdomains: SHD1, SHD2, and a zinc-binding subdomain that is flanked by the two SHDs. ^[6] SHD1 is folded into a 66 A ° long helix α1, and SHD2 is composed of three helices (α3–α5). SHD1 and SHD2 interact with each other by making a coiled coil between α1 and α3–α5. In this coiled coil, α3 and α5 interact with α1 in an antiparallel manner (also see fidure 2). The zinc-binding subdomain contains four short ß strands (ß1–ß4) and loops including three short helices (α2, h1, and h2). The two zinc ions (Zn1 and Zn2) are each coordinated by four conserved cysteine residues: and Cys92 for Zn1 binding, and Cys81, Cys84, Cys104, and Cys107 for Zn2 binding. ^[7]

spinqualitylabelsall models Final model of 2zet: Two Rab27B/Slac2-a complexes (A/C and B/D) ( Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

References

1. ↑ Kukimoto-Niino M, Sakamoto A, Kanno E, Hanawa-Suetsugu K, Terada T, Shirouzu M, Fukuda M, Yokoyama S. Structural basis for the exclusive specificity of Slac2-a/melanophilin for the Rab27 GTPases. Structure. 2008 Oct 8;16(10):1478-90. PMID:18940604 doi:10.1016/j.str.2008.07.014
2. ↑ http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zet
3. ↑ Kukimoto-Niino M, Sakamoto A, Kanno E, Hanawa-Suetsugu K, Terada T, Shirouzu M, Fukuda M, Yokoyama S. Structural basis for the exclusive specificity of Slac2-a/melanophilin for the Rab27 GTPases. Structure. 2008 Oct 8;16(10):1478-90. PMID:18940604 doi:10.1016/j.str.2008.07.014
4. ↑ http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zet
5. ↑ Kuroda TS, Ariga H, Fukuda M. The actin-binding domain of Slac2-a/melanophilin is required for melanosome distribution in melanocytes. Mol Cell Biol. 2003 Aug;23(15):5245-55. PMID:12861011
6. ↑ Fukuda M, Kuroda TS, Mikoshiba K. Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: implications of a tripartite protein complex for melanosome transport. J Biol Chem. 2002 Apr 5;277(14):12432-6. Epub 2002 Feb 20. PMID:11856727 doi:10.1074/jbc.C200005200
7. ↑ Kukimoto-Niino M, Sakamoto A, Kanno E, Hanawa-Suetsugu K, Terada T, Shirouzu M, Fukuda M, Yokoyama S. Structural basis for the exclusive specificity of Slac2-a/melanophilin for the Rab27 GTPases. Structure. 2008 Oct 8;16(10):1478-90. PMID:18940604 doi:10.1016/j.str.2008.07.014